Emerging evidence points to a "perfect storm" of profound, deleterious, seizure-driven suprapontine effects on brainstem-mediated cardiovascular and respiratory processes leading to Sudden Unexpected Death in Epilepsy (SUDEP). This fatal dysregulation is likely to be underpinned by structural (pre-existing seizure- damaged autonomic regulatory areas) and functional (neurotransmitter/neuromodulator) predispositions. A multi-disciplinary Center Without Walls (CWW), systems biology-based approach that assembles and leverages clinical, electrophysiological, biochemical, imaging, genetic and neuropathological expertise has the best potential to unlock SUDEP mechanisms and the role of suprapontine influences. The NINDS funded the Prevention and Risk Identification of SUDEP Mortality (PRISM) Project through exploratory grant 1P20- NS076965. The SUDEP Translational Research Alliance (SUTRA) is the next phase of PRISM and is a multi-center, multi-disciplinary consortium led by Case Western Reserve University and includes UCLA, Northwestern University in Chicago, New York University, Southern Illinois University, Legacy Research Institute, Oregon, University College London, University of North Texas and Columbia University. PRISM has built infrastructure, resources and protocols, and established genetics (203 SUDEP DNA samples), neuropathology (139 SUDEP brains) and multimodal seizure data repositories on >300 prospectively surveyed patients. We have generated preliminary genetic, neuropathology and physiological seizure data to leverage the hypothesis driven scientific projects of this application. The primary mission of the SUTRA Administrative Core is to oversee, co-ordinate, prioritize and facilitate CWW research activities and functioning. The organized plan will comprise an Informatics and Data Analytics Core and five scientific project U01s. Specific Aims for SUTRA are 1) to provide overall leadership, vision, expertise and direction in the CWW's mission of research, discovery and dissemination of new knowledge, through establishment and implementation of the SUTRA charter and regular review and revision of direction, 2) to facilitate communications and collaborations between Cores and research groups participating in SUTRA, 3) to report all Center activities and progress to NINDS, the Executive and Steering Committees and 4) to further develop and expand SUTRA research infrastructure (expanding its biorepositories, establishing a Pilot and Feasibility Program, a Mentorship Program and an Enrichment Program to foster awareness of the latest research trends and opportunities). SUTRA will optimize and streamline interfaces with local resources and national resources including Epi4K, Autism Brain Net, the North American SUDEP Registry, the SUDEP Institute and the Sudden Death in Childhood Program.

Public Health Relevance

Sudden Unexpected Death in Epilepsy (SUDEP) is responsible for ~5000 deaths per year in the USA and is a significant public health issue. The SUDEP Translational Research Alliance (SUTRA) is a unique consortium of basic and clinician scientists in the field who bring together clinical, electrophysiological, genetics and neuropathological expertise, and are poised to provide long awaited answers to some pressing questions.